Compared with Imuran, cyclosporine (CSA) and tacrolimus have reduced acute rejection rates in orthotopic liver transplant (OLTx) recipients to <50% but have well known toxicities e.g. hypertension, nephrotoxicity and neurotoxicity. Sirolimus (SRL, Wyeth Ayerst Research. Radnor, PA) is a potent T-cell inhibitor without such toxicities inhibits the effects of IL-2 receptor stimulation and is synergistic with cyclosporine which inhibits IL-2 production. In controlled phase II trials in renal transplantation, SRL has decreased rejection rates to <10% when combined with cyclosporine. Multicenter phase III trials evaluating low and high dose SRL with cyclosporine have reduced rejection rates to between 11-19%. Eight OLTx recipients are currently on SRL without rejection at a mean followup of 6.5 months.